The regulatory role of AP-2β in monoaminergic neurotransmitter systems: insights on its signalling pathway, linked disorders and theragnostic potential

Mohamed H Al-Sabri; Maryam Nikpour; Laura E Clemensson; Misty M Attwood; Michael J Williams; Mathias Rask-Anderson; Jessica Mwinyi; Helgi B Schiöth

doi:10.1186/s13578-022-00891-7

The regulatory role of AP-2β in monoaminergic neurotransmitter systems: insights on its signalling pathway, linked disorders and theragnostic potential

Cell Biosci. 2022 Sep 8;12(1):151. doi: 10.1186/s13578-022-00891-7.

Authors

Mohamed H Al-Sabri¹, Maryam Nikpour^{1

2}, Laura E Clemensson¹, Misty M Attwood¹, Michael J Williams¹, Mathias Rask-Anderson³, Jessica Mwinyi¹, Helgi B Schiöth⁴

Affiliations

¹ Department of Surgical Sciences, Division of Functional Pharmacology and Neuroscience, Biomedical Center (BMC), Uppsala University, Husargatan 3, P.O. Box 593, 75124, Uppsala, Sweden.
² Department of Medical Sciences, Uppsala University, BMC, Husargatan 3, 750 03, Uppsala, Sweden.
³ Department of Immunology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
⁴ Department of Surgical Sciences, Division of Functional Pharmacology and Neuroscience, Biomedical Center (BMC), Uppsala University, Husargatan 3, P.O. Box 593, 75124, Uppsala, Sweden. Helgi.schioth@neuro.uu.se.

Abstract

Monoaminergic neurotransmitter systems play a central role in neuronal function and behaviour. Dysregulation of these systems gives rise to neuropsychiatric and neurodegenerative disorders with high prevalence and societal burden, collectively termed monoamine neurotransmitter disorders (MNDs). Despite extensive research, the transcriptional regulation of monoaminergic neurotransmitter systems is not fully explored. Interestingly, certain drugs that act on these systems have been shown to modulate central levels of the transcription factor AP-2 beta (AP-2β, gene: TFAP2Β). AP-2β regulates multiple key genes within these systems and thereby its levels correlate with monoamine neurotransmitters measures; yet, its signalling pathways are not well understood. Moreover, although dysregulation of TFAP2Β has been associated with MNDs, the underlying mechanisms for these associations remain elusive. In this context, this review addresses AP-2β, considering its basic structural aspects, regulation and signalling pathways in the controlling of monoaminergic neurotransmitter systems, and possible mechanisms underpinning associated MNDS. It also underscores the significance of AP-2β as a potential diagnostic biomarker and its potential and limitations as a therapeutic target for specific MNDs as well as possible pharmaceutical interventions for targeting it. In essence, this review emphasizes the role of AP-2β as a key regulator of the monoaminergic neurotransmitter systems and its importance for understanding the pathogenesis and improving the management of MNDs.

Keywords: AP-2β; Diagnostic biomarker and therapeutic target; Dopamine; Monoamine neurotransmitter disorders; Monoaminergic neurotransmitter systems; Neuroblastoma; Noradrenaline; Obesity; Polymorphisms; Serotonin; TFAP2Β; Transcription factor AP-2 beta.

Publication types

Review